# Neoadjuvant cemiplimab for resectable stage II to IV skin squamous cell carcinoma

Source: https://onco.cc/trials/neoadjuvant-cemiplimab-cscc/  
OnCo record `neoadjuvant-cemiplimab-cscc` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Giving the immunotherapy before the operation left no living cancer cells in the removed specimen in half of the patients. For tumours that would otherwise cost someone an eye, an ear or part of the face, that changes what the operation has to take.

## Summary

The large, deeply invasive cutaneous squamous cell carcinomas that arise on the face and scalp of older people are curable by surgery, but the surgery can be disfiguring or can cost an eye. This trial asked whether shrinking them first with a PD-1 antibody would change what had to be removed.

Seventy-nine patients with resectable stage II to IV disease received up to four doses of cemiplimab 350 mg every three weeks and then went to surgery. The primary endpoint was a pathological complete response, meaning no viable tumour cells anywhere in the surgical specimen on independent central review, with a null hypothesis of 25 per cent.

A pathological complete response was found in 40 of 79 patients (51 per cent, 95 per cent confidence interval 39 to 62) and a pathological major response, defined as viable tumour making up 10 per cent or less of the specimen, in a further 10 (13 per cent, 6 to 22). Almost two-thirds of the specimens therefore contained little or no living cancer. Imaging responses, at 68 per cent (57 to 78), understated the pathological result, which is the usual pattern with immunotherapy and is the reason the pathologist rather than the scanner decides this endpoint. Adverse events of any grade during the study occurred in 69 patients (87 per cent) and grade 3 or higher in 14 (18 per cent).

What the trial does not yet answer is whether the surgery can be reduced, or omitted, on the strength of the response. It was designed with surgery for everybody, so the pathological complete responses were resected rather than watched. That is the next question, and it is the same question being asked after neoadjuvant immunotherapy in rectal and in bladder cancer.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-25
- Also known as: Gross neoadjuvant cemiplimab study; neoadjuvant cemiplimab in cutaneous squamous cell carcinoma
- Registry id: NCT04154943
- Phase: 2
- Setting: Resectable stage II, III or IV (without distant metastases) cutaneous squamous cell carcinoma: up to four doses of cemiplimab 350 mg every three weeks before surgery with curative intent, with pathological complete response on independent central review as the primary endpoint against a null hypothesis of 25 per cent
- Sponsor: Regeneron Pharmaceuticals and Sanofi
- Enrolled: 79
- Result: Pathological complete response in 40 of 79 patients (51 per cent, 95 per cent confidence interval 39 to 62) and pathological major response in a further 13 per cent, with grade 3 or higher adverse events in 18 per cent.
- Outcomes: Pathological complete response on independent review: Neoadjuvant cemiplimab, up to 4 doses 51%; Pathological major response on independent review: Neoadjuvant cemiplimab, up to 4 doses 13%; Objective response on imaging: Neoadjuvant cemiplimab, up to 4 doses 68%
- Replication: A pilot study of two doses of neoadjuvant cemiplimab produced the same high pathological complete response rate and is what this confirmatory phase 2 study was built to test.

## Sources

- ClinicalTrials.gov NCT04154943: https://clinicaltrials.gov/study/NCT04154943
- Primary report (New England Journal of Medicine 2022): https://doi.org/10.1056/NEJMoa2209813
- Primary report on PubMed: https://pubmed.ncbi.nlm.nih.gov/36094839/

## Connected records

- cancers: [Advanced cutaneous squamous cell carcinoma](https://onco.cc/cancers/advanced-cutaneous-scc/), [Cutaneous squamous cell carcinoma](https://onco.cc/cancers/cutaneous-scc/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Cemiplimab](https://onco.cc/drugs/cemiplimab/)
- companies: [Regeneron](https://onco.cc/companies/regeneron/), [Sanofi](https://onco.cc/companies/sanofi/)
- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/), [The margin in skin cancer surgery](https://onco.cc/terms/surgical-margins-keratinocyte-cancer/)
- trials: [C-POST (cemiplimab after surgery and radiotherapy for high-risk skin squamous cell carcinoma)](https://onco.cc/trials/c-post/), [EMPOWER-CSCC-1](https://onco.cc/trials/empower-cscc-1/), [KEYNOTE-629](https://onco.cc/trials/keynote-629/)
- key papers: [Neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma](https://onco.cc/key-papers/paper-gross-neoadjuvant-cemiplimab-cscc-nejm-2022/)

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